F2RL2 coagulation factor II thrombin receptor like 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: F2RL2provided by HGNC
Official Full Name: coagulation factor II thrombin receptor like 2provided by HGNC
Primary source: HGNC:HGNC:3539
See related: Ensembl:ENSG00000164220 MIM:601919; AllianceGenome:HGNC:3539
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: PAR3; PAR-3
Summary: This gene encodes a member of the protease-activated receptor (PAR) family which is a subfamily of the seven transmembrane G protein-coupled cell surface receptor family. The encoded protein acts as a cofactor in the thrombin-mediated cleavage and activation of the protease-activated receptor family member PAR4. The encoded protein plays an essential role in hemostasis and thrombosis. Alternate splicing results in multiple transcript variants that encode different isoforms. [provided by RefSeq, Feb 2012]
Expression: Biased expression in gall bladder (RPKM 4.3), endometrium (RPKM 1.5) and 10 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 5q13.3

Exon count:: 2

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (76615482..76623403, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (77097223..77105145, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (75911307..75919228, complement)

Chromosome 5 - NC_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

PAR3 is essential in thrombin stimulated insulin secretion.
Title: Thrombin stimulates insulin secretion via protease-activated receptor-3.
TFRGAP, a PAR-3 mimicking peptide significantly induced the phosphorylation of eNOS-Thr-495 with minimal phosphorylation of eNOS-Ser-1177 with no change in nitric oxide production.
Title: Featured Article: Differential regulation of endothelial nitric oxide synthase phosphorylation by protease-activated receptors in adult human endothelial cells.
These data provide intriguing novel insights into the diversification of functional selectivity of protease signaling achievable by canonical and noncanonical PAR activation, such as the activation of vascular-protective Tie2 by noncanonical PAR3 activation.
Title: Noncanonical PAR3 activation by factor Xa identifies a novel pathway for Tie2 activation and stabilization of vascular integrity.
In pancreatic adenocarcinoma cells, PAR3 knockdown enhances cell adhesion. We propose this is due to increased expression of E-cadherin, leading to a greater adhesion of free-floating cells to cells bound to the surface via integrins, particularly ITGalphav.
Title: PAR-3 knockdown enhances adhesion rate of PANC-1 cells via increased expression of integrinαv and E-cadherin.
Data indicate that knockdowns of all three PARs PAR-1, PAR-2, and PAR-3 exhibited changes in the expression of CDC42, which correlated with the changes in their invasion.
Title: Proteinase-activated receptors differentially modulate in vitro invasion of human pancreatic adenocarcinoma PANC-1 cells in correlation with changes in the expression of CDC42 protein.
Elevated expression of PAR-3, but not PAR-4, was detected in the lungs of idiopathic pulmonary fibrosis patients.
Title: Protease-activated receptors (PAR)-1 and -3 drive epithelial-mesenchymal transition of alveolar epithelial cells - potential role in lung fibrosis.
A unique contributory role for PAR3 in the complex mechanisms underlying Activated protein C cytoprotective effects.
Title: Novel mechanisms for activated protein C cytoprotective activities involving noncanonical activation of protease-activated receptor 3.
PAR-3 receptors interact with thrombin and increase heme oxygenase-1 expression in synovial fibroblasts.
Title: Thrombin induces heme oxygenase-1 expression in human synovial fibroblasts through protease-activated receptor signaling pathways.
Human PAR-3 is regulated post-transcriptionally via the mRNA-stabilizing factor HuR, whereas transcriptional control involves nuclear factor of activated T cells (NFAT).
Title: Regulation of human vascular protease-activated receptor-3 through mRNA stabilization and the transcription factor nuclear factor of activated T cells (NFAT).
FXa bound in a punctate manner to thrombi under shear, while thrombin and fibrin(ogen) distributed ubiquitously over platelet-fibrin thrombi
Title: Spatial distribution of factor Xa, thrombin, and fibrin(ogen) on thrombi at venous shear.

Submit: New GeneRIF Correction See all GeneRIFs (32)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
A genome-wide association study for age-related hearing impairment in the Saami. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Vif	vif	HIV-1 Vif downregulates the expression of coagulation factor II (thrombin) receptor-like 2 (F2RL2) in Vif-expression T cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:483135

D11S3114 (e-PCR)
- UniSTS:152207

STS-N26732 (e-PCR)
- UniSTS:64186

NoName (e-PCR)
- UniSTS:480739

F2RL2_622 (e-PCR)
- UniSTS:277222

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables G protein-coupled receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables G protein-coupled receptor activity	TAS Traceable Author Statement more info
enables phosphatidylinositol phospholipase C activity	TAS Traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables receptor ligand activity	IEA Inferred from Electronic Annotation more info
enables thrombin-activated receptor activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in G protein-coupled receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in blood coagulation	TAS Traceable Author Statement more info	PubMed
involved_in ligand-gated ion channel signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in platelet activation	TAS Traceable Author Statement more info
involved_in positive regulation of insulin secretion	IEA Inferred from Electronic Annotation more info
involved_in response to wounding	TAS Traceable Author Statement more info	PubMed
involved_in thrombin-activated receptor signaling pathway	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in apical plasma membrane	IEA Inferred from Electronic Annotation more info
located_in extracellular region	TAS Traceable Author Statement more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	TAS Traceable Author Statement more info
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: proteinase-activated receptor 3

Names: Coagulation factor II receptor-like 2 (protease-actovated receptor 3); protease-activated receptor 3; thrombin receptor-like 2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001256566.2 → NP_001243495.1 proteinase-activated receptor 3 isoform 2

See identical proteins and their annotated locations for NP_001243495.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate exon in the 5' UTR and coding region, compared to variant 1. These differences cause translation initiation at a downstream AUG and result in an isoform (2) with a shorter N-terminus, compared to isoform 1.

Source sequence(s)

AC026725, AK298585, AL048674

Consensus CDS

CCDS58959.1

UniProtKB/TrEMBL

Q4VBN6

Related

ENSP00000426703.1, ENST00000504899.1

Conserved Domains (1) summary

cd15371
Location:73 → 346

7tmA_PAR3; protease-activated receptor 3, member of the class A family of seven-transmembrane G protein-coupled receptors
NM_004101.4 → NP_004092.1 proteinase-activated receptor 3 isoform 1 precursor

See identical proteins and their annotated locations for NP_004092.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AC026725, AL048674, BC093650, DC419029

Consensus CDS

CCDS4031.1

UniProtKB/Swiss-Prot

B2R754, B4DQ13, O00254, Q52M68, Q7Z3W3

UniProtKB/TrEMBL

Q4VBN6

Related

ENSP00000296641.3, ENST00000296641.5

Conserved Domains (1) summary

cd15371
Location:95 → 368

7tmA_PAR3; protease-activated receptor 3, member of the class A family of seven-transmembrane G protein-coupled receptors